chr4-5416859-A-G

Variant names:

• chr4-5416859-A-G
• rs796052163
• NM_018401.3:c.487A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_018401.3(STK32B):​c.487A>G​(p.Thr163Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK32B NM_018401.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.21
• Publications: 1 publications found

Genes affected

STK32B (HGNC:14217): (serine/threonine kinase 32B) This gene encodes a serine-threonine protein kinase. Serine-threonine kinases transfer phosphate molecules to the oxygen atoms of serine and threonine. A genomic deletion affecting this gene has been associated with Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-5416859-A-G is Benign according to our data. Variant chr4-5416859-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 207871.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018401.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32B	NM_018401.3	MANE Select	c.487A>G	p.Thr163Ala	missense	Exon 6 of 12	NP_060871.1	Q9NY57-1
	STK32B	NM_001306082.2		c.346A>G	p.Thr116Ala	missense	Exon 7 of 13	NP_001293011.1	Q9NY57-2
	STK32B	NM_001345969.2		c.472+18615A>G		intron	N/A	NP_001332898.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32B	ENST00000282908.10	TSL:1 MANE Select	c.487A>G	p.Thr163Ala	missense	Exon 6 of 12	ENSP00000282908.5	Q9NY57-1
	STK32B	ENST00000510398.1	TSL:1	c.346A>G	p.Thr116Ala	missense	Exon 6 of 12	ENSP00000420984.1	Q9NY57-2
	STK32B	ENST00000512018.5	TSL:1	n.*441A>G		non_coding_transcript_exon	Exon 7 of 13	ENSP00000422820.1	D6R9Y2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.18	N
PhyloP100		5.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.21
Sift	Benign	0.038	D
Sift4G	Benign	0.11	T
Polyphen		0.19	B
Vest4		0.70
MutPred		0.66		Loss of sheet (P = 0.1907)
MVP		0.56
MPC		0.12
ClinPred		0.69	D
GERP RS		4.6
Varity_R		0.33
gMVP		0.63
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796052163; hg19: chr4-5418586;